The roles of morphogenetic differentiation in controlling the phenotypic expression of neoplastic transformation, the degree of malignancy of tumors, and the susceptibility of developing organs to carcinogenesis are studied using organ culture and tissue transplantation techniques, with current emphasis on the kidney. A defined medium for growth of rat and mouse ureteric bud epithelium in monolayer culture has been developed in which epiderman growth factor and selenium have proved essential and insulin, hydrocortisone, and transferrin have proved highly beneficial. The ability of transplacentally administered carcinogens to induce genotoxic damage in cells of embryos or fetuses exposed at different stages of gestation was determined for rat, mouse, and Syrian hamster. Cells were isolated from exposed embryos and gene mutations at two to three loci (resistance to ouabain and 6-thioguanine, and to diptheria toxin in the hamster) were assayed in vitro with simultaneous determination of survival ability. Organ specificity of induced gene mutation is being determined in embryonal cells isolated from organs of various species exposed in utero at comparable stages of gestation. Quantitative dose curves for transplacentally induced mutations were also obtained for selected carcinogens, including the polycyclic hydrocarbons, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzo[a]pyrene, the nitroso compounds, N-nitrosoethyl (and methyl) urea and N-nitrosodiethylamine, ethyl carbamate, and methyl (and ethyl) methane sulfonate.